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Methylation quantitative trait locus (meQTL) analysis of osteoarthritis links epigenetics with genetic risk

Lookup NU author(s): Dr Michael Rushton, Dr Louise Reynard, Professor David YoungORCiD, Dr Colin Shepherd, Dr Fiona Gee, Dr Rebecca Darlay, Professor David Deehan, Professor Heather Cordell, Professor John LoughlinORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Osteoarthritis (OA) is a common, painful and debilitating disease of articulating joints resulting from the age-associated loss of cartilage. Well-powered genetic studies have identified a number of DNA polymorphisms that are associated with OA susceptibility. Like most complex trait loci, these OA loci are thought to influence disease susceptibility through regulation of gene expression, so called expression quantitative loci, or eQTLs. One mechanism through which eQTLs act is epigenetically, by modulating DNA methylation. In such cases, there are quantitative differences in DNA methylation between the two alleles of the causal polymorphism, with the association signal referred to as a methylation quantitative trait locus, or meQTL. In this study, we aimed to investigate whether the OA susceptibility loci identified to date are functioning as meQTLs by integrating genotype data with whole genome methylation data of cartilage DNA. We investigated potential genotype-methylation correlations within a 1.0-1.5 Mb region surrounding each of 16 OA associated single nucleotide polymorphisms (SNPs) in 99 cartilage samples, and identified four that function as meQTLs. Three of these replicated in an additional cohort of up to 62 OA patients. These observations suggest that OA susceptibility loci regulate the level of DNA methylation in cis and provide a mechanistic explanation as to how these loci impact upon OA susceptibility, further increasing our understanding of the role of genetics and epigenetics in this common disease.

Publication metadata

Author(s): Rushton MD, Reynard LN, Young DA, Shepherd C, Aubourg G, Gee F, Darlay R, Deehan D, Cordell HJ, Loughlin J

Publication type: Article

Publication status: Published

Journal: Human Molecular Genetics

Year: 2015

Volume: 24

Issue: 25

Pages: 7432-7444

Print publication date: 20/12/2015

Online publication date: 13/10/2015

Acceptance date: 09/10/2015

Date deposited: 24/11/2015

ISSN (print): 0964-6906

ISSN (electronic): 1460-2083

Publisher: Oxford University Press


DOI: 10.1093/hmg/ddv433

PubMed id: 26464490


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Funder referenceFunder name
Arthritis Research UK
Arthritis Research UK as part of the MRC-Arthritis Research UK Centre for Integrated Research into Musculoskeletal Ageing (CIMA)
NIHR Newcastle Biomedical Research Centre
Medical Research Council
305815European Union